Relationship between Genetic Risk and Age of Diagnosis of Systemic Lupus Erythematosus

OBJECTIVE: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis. METHODS: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population. RESULTS: The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r² = 0.175 for GRWS; P = 0.008 and r² = 0.178 for GRSCS; P = 0.002 and r² = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r² = 0.176 for GRCS; P = 0.022 and r² = 0.176 for GRWS; P = 0.022 and r² = 0.176 for GRSCS; P = 0.011 and r² = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis). CONCLUSION: Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.